Microwave-assisted allylations in distilled water and its reaction mechanism

Xu Xiaolan, Hui Ailing, Zhou Cunliu, Zha Zhenggen, Wang Zhiyong
(Department of Chemistry, University of Science & Technology of China, Hefei 230026)

Received Mar. 16, 2005; Supported by the National Natural Science Foundation of China (50073021) and National Natural Science Foundation of Anhui Province (01046301).

Abstract  Microwave Irradiation（MWI）was applied in the allylations of carbonyl compounds in water firstly. In the presence of mediator (Zn/SnCl₂) MWI can promote the allylation greatly. Also, the allylation of carbonyl compounds with unactive allyl chloride in water was realized under MWI. The ketones that hardly allylate with allyl halide (Br or Cl) proceeded the allylation smoothly by using MWI to give the corresponding product in good yield. Compared with the traditional aqueous allylation, the reaction yield was improved greatly and the reaction time was reduced dramatically.
Keywords Aromatic aldehydes, Water, Catalysis, Halides, Allylation

Homoallylic alcohols are well known as important building blocks in many biological active molecules such as macrolides, polyether and antibiotics ^[1]. Recently a variety of aqueous Barbier-reactions were developed to give the homoallylic alcohols. However, the reactions normally take longer time ^[2] and a variety of assistant agents ^[3] were often involved. Particularly, the allylations of some ketones in water hardly occur in catalytic amount of auxiliary agents such as Lewis acids and mediators ^[4]. Therefore, how to promote Barbier reaction in net water becomes one of the crucial points in the aqueous allylations. As far as we know, microwave irradiation (MWI) plays an important role in organic reactions ^[5]. One of the features from MWI is to reduce the reaction time from days or hours to minutes or seconds. Secondly, microwave heating in the sealed reaction vessels is a highly efficient heating technique. Besides, the heating procedure is easily controlled since the energy input starts and stops immediately when the power is turned on or off. So far, MWI has been employed in organic reactions such as Heck–reaction ^[6], Suzuki reaction ^[7] and other reactions ^[8] to enhance the reaction efficiency, giving the excellent results. Moreover, a few reports ^[9] about microwave-assisted reaction in aqueous media were published recently. However, there is no report about microwave-assisted allylation of carbonyl compound in water yet. In order to enhance the allylation efficiency, MWI was employed in the allylation in our lab. As a result, the corresponding homoallylic alcohols were obtained in high yield and the reactions were finished in a short reaction time. Herein, we wish to report zinc-mediated allylations of carbonyl compounds with allyl halide (Cl and Br) in distilled water via MWI.
    First of all, the microwave power and the irradiation time were optimized. When the general microwave oven is applied in the organic reaction, the microwave power is in the range of 100-400W and the irradiation time is several minutes. In our experiments such as the reaction of benzaldehyde with allyl bromide (Scheme 1), the best reaction condition is 300W for the microwave power and 30-45second for the irradiation time, while the other conditions, such as the power is 80w, 150w, 450w and the irradiation time is 15s, 60s and 90s respectively, afford the corresponding products in a lower yield of 30-60%. On the base of this optimization, different Lewis acids were employed in the allylation respectively. The experimental results were listed in Table 1.

Scheme 1

Table 1 Allylation of benzaldehyde with allylic bromide under different condition


    From Table 1 it was found that stannous dichloride is the most efficient to mediate the allylation under the microwave, giving the highest yield of 93% (entry1, Table 1). In comparison with the allylation without microwave, the yields were enhanced greatly and the reaction time was shortened absolutely. Under microwave condition, moreover, the dosage of SnCl₂ plays a crucial role in the allylation. The optimized dosage is 0.2 equivalent of SnCl_2. Neither more nor less than 0.2 equivalent of SnCl₂ gives a good result.
    Then the allylations of different aldehydes and ketones with allyl bromide were carried out under the optimized condition (Scheme 2). The results were listed in Table 2. From which, it was found that allylation under microwave gave higher yields and shorter reaction time than the allylations without microwave.

Scheme 2


Table 2 Allylation of different carbonyl compounds in distilled water

    This result intrigued us to substitute allyl bromide with allyl chloride in order to enlarge organic reactions in water. The allylation by allyl chloride will be more interesting since allyl chloride is more popular and cheaper chemical raw material. To the best of our knowledge, however, the allylation by allyl chloride hardly occurs in water since the energy of C-Cl bond is higher than that of C-Br bond. In fact, under the same condition, the allylation by allyl chloride gave lower yield. Therefore the auxiliary agent is necessary to be used to enhance the allylation by allyl chloride. Usually, phase transfer catalyst (PTC) is effective to activate C-Cl bond ^[10]. After a lot of trials, tetrabutyl ammonium bromide was chosen as a PTC to catalyze the allylation, giving the best result.
    Therefore the mediator system for the allylation by allyl chloride was optimized as Zn (1.5mol)-SnCl₂ (0.2mol)-Bu₄NBr (0.1mol) under MWI. Under this condition, the allylations of different aldehydes and ketones with allyl chloride were carried out in water. The experimental results and the comparisons with the conventional allylation were listed in Table 2.
    From Table 2, it was found that some aldehydes such as benzaldehyde, 4-chloro-benzaldehyde and 4-methyl-benzaldehyde reacted with allyl chloride smoothly to give the corresponding adducts in good yields, while the allylations without the MWI gave the corresponding product in lower yields and the reactions took long time (entries 1-6, Table 2). Particularly, the allylation of 2-hydroxyl-benzaldehyde gave the corresponding product in good yield without tedious protection and deprotection of hydroxyl group under the condition (entries 7 and 8, Table 2). As for 4-chloro-benzyl acetone and cyclohexanone, the allylations gave the corresponding alcohols in very low yield and took longer reaction time without MWI. Under MWI, however, the allylations of ketones give the corresponding adducts in good yields and reaction time was shortened from 20-24 h to 2 minutes (entries 15, 16, 19 and 20, Table 2). In a word, the employment of the microwave in the allylation enhanced the reaction yield greatly and shortened the reaction time dramatically.
    The mechanism of organic reaction accelerated by MWI is very complicate. Here two factors from MWI affect the reaction. One is the heat effect ^[11], which can increase the kinetic energy of the reactant molecules so that the probability of collision among molecules is enhanced, resulting in improvement of the reaction. The other is non-heat effect ^[12], which maybe plays more important role in the reaction than the heat effect. Normally, non-heat effect affects the reaction by changing the reaction path, resulting in the reduction of the reaction active energy. As a result, the reaction rate is enhanced dramatically and the reaction yield is improved. Here, in this bimetal mediation system, Zn transferred the electron to Sn²⁺ firstly and reduced Sn²⁺ to Sn (0). Then in-situ Sn (0) inserted in the C-Br bond of the allyl bromide, resulting in the formation of allyltin halide (1). In conventional allylation, this polar organotin compound (1) should attack the nucleophilic center in the aldehyde to give rise to the corresponding addition product. However, under MWI, (1) was irradiated mostly because of the strong polarity of this molecule, leading to the formation of the allyl radical (2). On the other hand, Zn can transfer the electron to the aldehyde to afford radical anion (3), which can connect (2) to generate the corresponding homoallylic alcohol (4) after capturing a proton in water. In this way, the reaction active energy was reduced largely, as shown in scheme 3.

Scheme 3

    Actually, we obtained Zn(OH)X and Sn(OH)X (X=Br, Cl) from the white precipitation and gray precipitation respectively. Also, some hexa-1, 5-diene was observed. These experimental facts supported the mechanism proposed here. As a result, the reaction time was reduced dramatically and the reaction yield was increased because the reaction path was changed from nucleophilic addition to radical polymerization. As for allyl chloride, the insertion of tin into the C-Cl bond is difficult because of the shorter bond length and higher bond energy of C-Cl bond in comparison with the C-Br bond. In the presence of tertrabutyl ammonium bromide (PTC), the polarity of the C-Cl bond can be enhanced by the action of PTC so that tin can insert this bond to afford the allyltin halide (1). Then the reaction followed the scheme 3, realizing the allylation of carbonyl compound with allyl chloride.
    In conclusion, the microwave was applied into the allylations of carbonyl compounds in water firstly. A novel bimetal mediation system, Zn-SnCl₂-MW, was employed in the allylations. The reaction yields were improved greatly and the reaction time was reduced dramatically. Also, the reaction mechanism under the MWI was studied. Experimental results indicated that the reaction path was changed from nucleophilic addition to radical polymerization. Therefore MWI improved the allylations via changing the reaction path. This result will intrigue us to improve the other reactions and develop new reactions by using MWI further. The extensive application of MWI is in progress at our laboratory.

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